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Biomedical subjects

D Goldschmidt

Publications and source records attributed to D Goldschmidt.

At least 19 recordsLinked to original sources
PubMed2004

Glucose-6-phosphate dehydrogenase activity in male premature and term neonates.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term neonates than in adults. Some studies have suggested that activity may be even higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in preterm than term neonates, and whether higher activity would interfere with diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was determined in the first 48 hours after delivery in male premature, term, and near term infants. G6PD deficient neonates were separated, and the remaining premature infants compared with healthy, male, G6PD normal, near term and term neonates. RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8) weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g haemoglobin (Hb), which is clearly in the deficient range with no overlap into the normal range. G6PD activity in the remaining premature infants was significantly higher than in 24 near term and term neonates (gestational age > or = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that significance was limited to those born between 29 and 32 weeks gestation, in which group G6PD activity was significantly higher than in those born before 29 weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation. CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32 weeks gestation than in term neonates. This did not interfere with diagnosis of G6PD deficiency.

Gestational Age↗
PubMed2002

Protective effect of bilirubin in ischemia-reperfusion injury in the rat intestine.

BACKGROUND: Although bilirubin, which crosses the blood-brain barrier, can cause irreversible brain damage, it also possesses antioxidant properties that may be protective against oxidative stress. Intestinal ischemia-reperfusion (IR) injury results in cell destruction, mediated via the generation of reactive oxygen species. Although increased serum bilirubin is correlated with increased antioxidant potential in the face of hyperoxia, evidence of bilirubin-associated protective effect against IR injury remains nonspecific. We therefore sought to investigate whether hyperbilirubinemia would be protective against IR injury to the intestine. METHODS: Young adult rats were randomly assigned to one of three groups: 1) IR/control (n = 12); 2) IR/hyperbilirubinemia (n = 10), in which IR was generated while the rats were treated with a continuous infusion of bilirubin; and 3) hyperbilirubinemia controls (n = 10). Blood and intestinal tissue samples were obtained to determine serial thiobarbituric acid reducing substances (index of lipid peroxidation) and for xanthine oxidase/xanthine dehydrogenase and glutathione/glutathione disulfide ratios. Intestinal histopathology was graded from 1 (normal) to 4 (severe necrotic lesions). RESULTS: Histopathologic scoring and circulating and tissue thiobarbituric acid reducing substances were highest in the IR/control animals compared with either the IR/hyperbilirubinemics or the controls. All of these are consistent with the most severe injury in this group. Xanthine oxidase/xanthine dehydrogenase ratios were not significantly different among the groups. CONCLUSION: Hyperbilirubinemia ameliorates the extent of intestinal IR injury in our model and appears to act as an antioxidant. This study supports the concept that bilirubin possesses some beneficial properties in vivo, although no direct clinical conclusions can be drawn from these data.

Animals↗
PubMed2001

Processing in the C-terminal domain of minicollagen XII removes a heparin-binding site.

A minicollagen comprising the two C-terminal domains of collagen XII (COL1 and NC1) has been expressed in insect cells and characterized biochemically. An interaction with heparin is demonstrated, which depends on the correct folding of the molecule. After secretion, minicollagen XII is immediately processed to a form lacking heparin binding ability. Processed and unprocessed trimers differ only at the level of the eight or nine C-terminal residues but they reveal different structures as judged from rotary shadowing images. Similar processing is also observed in the medium of transfected human HeLa cells. These data show that a heparin-binding site is present in the C-terminal end of the chicken collagen XII sequence and strongly suggest that proteolytic processing in the NC1 domain can occur in vivo and regulate the interactive properties of collagen XII.

Amino Acid Sequence↗
PubMed2001

Collagenous sequence governs the trimeric assembly of collagen XII.

A minicollagen containing the COL1 and NC1 domains of chicken collagen XII has been produced in insect cells. Significant amounts of trimers contain a triple-helical domain in which the cysteines are not involved in inter- but in intrachain bonds. In reducing conditions, providing that the triple-helix is maintained, disulfide exchange between intra- and interchain bonding is observed, suggesting that the triple-helix forms first and that in favorable redox conditions interchain bonding occurs to stabilize the molecule. This hypothesis is verified by in vitro reassociation studies performed in the presence of reducing agents, demonstrating that the formation of interchain disulfide bonds is not a prerequisite to the trimeric association and triple-helical folding of the collagen XII molecule. Shortening the COL1 domain of minicollagen XII to its five C-terminal GXY triplets results in an absence of trimers. This can be explained by the presence of a collagenous domain that is too short to form a stable triple-helix. In contrast, the presence of five additional C-terminal triplets in COL1 allows the formation of triple-helical disulfide-bonded trimers, suggesting that the presence of a triple-helix is essential for the assembly of collagen XII.

Amino Acid Sequence↗
PubMed2001

Munchausen syndrome.

Munchausen syndrome is a rare condition in which the patient repeatedly seeks medical care for factitious illnesses. With this self-inflicted disease, the patients characteristically travel from one hospital to another, feigning acute, usually spectacular illnesses. The patients willingly submit themselves to extensive as well as invasive diagnostic and therapeutic procedures. Munchausen syndrome is a psychiatric disorder that requires psychiatric treatment. Reconstructive surgical procedures may be required to correct the acquired deformities. The difficulty in Munchausen syndrome lies essentially in early recognition of the psychiatric syndrome. Two exceptional cases are reported, and diagnosis and treatment are presented in the light of the current literature.

Adult↗
PubMed2001

Complete phalloplasty using the free radial forearm flap for correcting micropenis associated with vesical exstrophy.

PURPOSE: We present a new surgical technique for reconstructing the penis in a man with micropenis associated with vesical exstrophy. MATERIALS AND METHODS: A free radial forearm flap was used to create a penis of normal length and diameter. The flap was wrapped around the native micropenis. A penile prosthesis was then inserted in the flap to provide erection. RESULTS: The flap was well vascularized and no skin damage was observed 6 years after reconstruction. The patient achieved sexual intercourse on a regular basis. He is satisfied with the result. CONCLUSIONS: Free transfer of the radial forearm flap may be done in select men with micropenis associated with vesical exstrophy for penile reconstruction. An inflatable prosthesis may be inserted in the flap to provide erection. The results of this technique have remained stable in the long term. This method provides a new tool for phalloplasty in these difficult cases.

Adult↗
PubMed2000

Negative side-effects of retention sutures for abdominal wound closure. A prospective randomised study.

OBJECTIVE: To assess the effect of retention sutures on the postoperative course of patients after major abdominal operations. DESIGN: Prospective, randomised study. SETTING: Teaching hospital, Germany. SUBJECTS: 95 patients who were at increased risk of wound failure after major abdominal operations. INTERVENTION: Conventional mass closure either with (n = 44) or without (n = 51) reinforcement by wire retention sutures. MAIN OUTCOME MEASURES: Pain intensity on postoperative days 3, 6, 9, and 12, patients' acceptance, retention-suture-related morbidity, general morbidity. RESULTS: Postoperative pain was overall more severe with retention sutures. On day 6, 31/49 control patients but only 13/41 patients with retention sutures were pain-free (p = 0.003, 95% CI 0.12 to 0.51). Twelve of 44 patients with retention sutures developed local complications of the sutures, and 21 of the 44 had to have them removed prematurely, in most cases because of intolerable pain. CONCLUSIONS: Retention sutures used to close abdominal wounds cause inconvenience, pain, and specific morbidity.

Abdominal Muscles↗
PubMed1999

Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase.

BACKGROUND: Intestinal ischemia-reperfusion (IR) injury results in cell destruction, which may be mediated by the generation of reactive oxygen species, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can improve capillary flow and tissue oxygenation. Because of these combined effects, it has been hypothesized that pentoxifylline would protect against intestinal IR. METHODS: Young adult rats were randomly assigned to one of four experimental groups: IR/Placebo (n = 12) in which superior and inferior mesenteric arteries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in which IR was induced as in the Placebo group, but with 25 mg/kg PTX at 0, 30, and 60 minutes; No IR/Placebo (n = 12); and No IR/PTX (n = 6) in which placebo and PTX were applied with no IR. Blood and intestinal samples were taken for serial thiobarbituric acid-reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase-xanthine dehydrogenase ratios, glutathione, myeloperoxidase, and histopathology. RESULTS: Animals in the IR/PTX group had lower TBARS and the least severe histopathologic injury. Xanthine oxidasexanthine dehydrogenase ratios were elevated only in IR/ Placebo (0.67+/-0.22 vs. 0.45+/-0.14 in IR/PTX; 0.42+/-0.22 in No IR/Placebo; and 0.40+/-0.11 in No IR/PTX; p = 0.0009). Reduced glutathione was diminished in IR/PTX animals (38.9 +/-1.35 vs. 46.1+/-7.0 in IR/Placebo; 41.1+/-2.5 in No IR/ Placebo; 43.6+/-1.0 in No IR/PTX; p = 0.048). No differences were recorded in myeloperoxidase levels among groups. CONCLUSIONS: Pentoxifylline ameliorates histopathologic signs of injury and decreases lipid peroxidation (TBARS). Normal xanthine oxidase-xanthine dehydrogenase ratios in the treated compared with IR-only animals imply that the protective effect of PTX is at least partially mediated through inhibition of xanthine oxidase.

Animals↗
PubMed1998

Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region.

Fibromodulin belongs to the family of small, leucine-rich proteoglycans which have been reported to interact with collagens and to inhibit type I collagen fibrillogenesis. Decorin and fibromodulin exhibit a noticeable degree of sequence similarity. However, as previously reported [Font, B., Eichenberger, D., Rosenberg, L. M. & van der Rest, M. (1996) Matrix Biol. 15, 341-348] the domains of these molecules implicated in the interactions with type XII and type XIV collagens are different, these being the dermatan sulphate/chondroitin sulphate chain for decorin and the core protein for fibromodulin. At the present time the fibromodulin domains implicated in the interactions with fibrillar collagens remain unknown. In experiments reported here, we have sought to identify the structural requirements for fibromodulin interaction with collagen and for the control of type I collagen fibrillogenesis. Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s). In addition, we show that the binding of fibromodulin (or fibromodulin-derived fragments) to type I collagen is not necessarily correlated with fibrillogenesis inhibition. To isolate fibromodulin domains, the native proteoglycan was submitted to mild proteolysis. We have isolated an alpha-chymotrypsin-resistant fragment which contains the bulk of the N-terminal and central region of the molecule including the leucine-rich repeats 4 and 6 reported for decorin to be involved in type I collagen binding. This fragment does not bind to type I collagen. Using enzymes with different specificities, a number of large fragments of fibromodulin were obtained, suggesting a compact structure for this molecule which is relatively resistant to proteolysis. None of these N-glycosylated fragments were able to bind to type I collagen in co-sedimentation experiments. Taken together these results suggest that fibromodulin-type I collagen interactions leading to fibrillogenesis inhibition require more than one binding domain. One of these domains could be the C-terminal end of the molecule containing the disulphide loop which is absent in the chymotrypsin-resistant fragment.

Amino Acid Sequence↗
PubMed1998

The in vitro influence of eight hormones and growth factors on the proliferation of eight sarcoma cell lines.

Little is known about the regulation of sarcoma proliferation by hormones and/or growth factors. We therefore characterised the in vitro proliferative influence on eight sarcoma cell lines of the platelet-derived growth factor, the insulin-like growth factor 1, triiodothyronine, the epidermal growth factor, the luteinising-hormone-releasing hormone, progesterone, gastrin and 17 beta-oestradiol. The influence of the different factors on the proliferation of sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a nutritionally poor medium containing 2% of fetal calf serum and (2) a nutritionally rich one containing 5% or 10% FCS both with and without the addition of non-essential amino acids. The results were analysed either by conventional statistical analyses or by a classification method based on a decision-tree approach developed in Machine Learning. This latter method was also compared to other classifiers (such as logistic regression and k nearest neighbours) with respect to its accuracy of classification. Monovariate statistical analysis showed that each of the eight cell lines exhibited sensitivity to at least one factor, and each factor significantly modified the proliferation of five or six of the eight cell lines under study. Of these eight lines one of fibrosarcoma origin was the most "factor-sensitive". Decision-tree-related data analysis enabled the specific pattern of factor sensitivity to be characterised for the three histological types of cell line under study. The effects of hormone and growth factors are significantly influenced by the type of culture medium used. The method used appeared to be an accurate classifier for the kind of data analysed. Sarcoma proliferation can be modulated, at least in vitro, by various hormones and growth factors, and the proliferation of each histopathological type exhibited a distinct sensitivity to different hormone and/or growth-factors.

Cell Division↗
PubMed1998

Traumatic spinal accessory nerve palsy.

Spinal accessory nerve sections due to a purely traumatic origin are very rare. The authors report a case in which a total section of the spinal accessory nerve was observed after a glass-penetrating injury. The primary lesion was undiagnosed, and only late physical examination revealed a scapula alata with a deficiency in shoulder protrusion and elevation. Surgical exploration with direct suturing of the nerve was performed 2 months after the initial trauma; full restoration of muscle function was obtained 12 months after the surgical procedure. Pain, the dominant preoperative feature, totally disappeared after restoration of shoulder function. Although infrequent, spinal accessory nerve lesions must always be excluded in cases of penetrating injuries in the posterior triangle of the neck. Emphasis is placed on diagnosis and treatment of this condition.

Accessory Nerve↗
PubMed1998

Free-flap evolution after hyperthermic regional chemotherapy in the isolated limb for malignant melanoma.

Two patients presenting with a stage I melanoma of the sole of the foot (Clark's level IV, Breslow's 2.8 mm, and Clark's level IV, Breslow's 3.2 mm) underwent a 3-cm tumor free-margin skin resection, followed by microanastomosed muscle flap reconstruction (serratus anterior and latissimus dorsi). Immediately after primary wound healing, an elective inguino-iliac lymph-node dissection, followed by hyperthermic isolated regional chemotherapy with Melphalan, was carried out. Only moderate swelling of both free flaps was observed after these procedures, and this resolved rapidly. The patients returned to ambulation after 2 weeks. No other side effects of the hyperthermic isolated regional chemotherapy were observed in the previously microanastomosed flaps.

Antineoplastic Agents, Alkylating↗
PubMed1997

Cutaneous necrotizing vasculitis after low dose methotrexate therapy for rheumatoid arthritis: a possible manifestation of methotrexate hypersensitivity.

Large haemorrhagic and necrotic cutaneous lesions developed after two low dose (5 mg) methotrexate injections in a patient suffering from long standing rheumatoid arthritis. Differential clinical diagnosis included factitia dermatitis, infectious processes, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, necrotizing arteritis and vasculitis. Histological and direct immunofluorescent examinations of skin biopsies supported the diagnosis of leucocytoclastic vasculitis. We discuss the respective roles of methotrexate and rheumatoid arthritis in the outbreak of leucocytoclastic vasculitis. Hypersensitivity is strongly suspected.

Antirheumatic Agents↗
PubMed1997

Verrucous carcinoma or epithelioma cuniculatum plantare.

Verrucous carcinoma is a rare form of squamous cell carcinoma. It behaves as a slow-growing, locally aggressive and rarely metastasizing tumour. Three clinical cases are presented, with emphasis on clinical presentation, pathological diagnosis and therapeutic approach. The pathogenesis of verrucous carcinoma, including chronic inflammation and human papillomavirus, is also discussed.

Aged↗
PubMed1997

In vitro characterization of lectin-induced alterations on the proliferative activity of three human melanoma cell lines.

Lectin binding is known to be able to elicit signalling events relevant for various aspects of cell physiology. The influence of lectin binding on melanoma cells remains relatively unexplored. The aim of our study was to investigate the in vitro effects of five plant lectins, namely peanut (PNA), wheat germ (WGA), concanavalin A (Con-A), Griffonia simplicifolia (GSA-IA4) and Phaseolus vulgaris (PHA-L) agglutinins, on the cell proliferation of melanoma cell lines (SK-MEL-28, HT-144 and C32) cultured in media supplemented with either 10% or 1% fetal calf serum (FCS). Cell proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. Four lectin concentrations were tested, namely 0.05, 0.5, 5 and 50 micrograms/ml, in four experimental settings, namely 1, 3, 5 and 7 days after the addition of each lectin to the culture media. Determination of the cell gain compartment (percentage of cells in the S and G2 phases of the cell cycle) was done by means of digital cell image analysis assessed on Feulgen-stained nuclei. Our results demonstrated that of the five lectins under study, four had a globally significant dose-dependent toxic effect on melanoma cell proliferation. The fifth lectin, PNA, had a significant stimulatory effect on the C32 cell line. Low doses of lectins may produce a transient increase in cell proliferation. Increasing the FCS from 1% to 10% in the culture media significantly antagonized lectin-induced toxicity in the three cell lines. The cell kinetics measurements showed that the inhibition of cell growth was merely due to cell death. The present data strongly suggest that some lectins might influence the proliferation of melanoma cells. In addition, because lectins are present in our diet and are able to pass into the systemic circulation, we speculate that lectins may exert an influence on melanoma growth under clinical conditions.

Cell Division↗
PubMed1997

Correlation between gender and cytomorphonuclear characteristics in human melanomas and in vitro evidence of sex steroid-induced modifications in the morphonuclear characteristics of three human melanoma cell lines.

The influence of gonadal steroids on human melanoma still remains a controversial issue. The aim of our study was to investigate whether sex steroids may influence the biological characteristics of human melanoma. Such biological characteristics were monitored at the morphological level by means of computer-assisted microscope analysis of Feulgen-stained nuclei, which provides 28 quantitative variables describing the nucleus morphometry (size, anisonucleosis level) and chromatin pattern. This methodology was used to characterize the morphonuclear features in a series of 69 human melanomas (from formalin-fixed paraffin embedded tissues) including 28 male, 17 premenopausal and 24 postmenopausal female patients, and to investigate the effect of two sex steroids (5-alpha-dihydrotestosterone [DHT] and 17-beta-oestradiol [E2]) on three human melanoma in vitro models--the HT-144, SK-MEL-28 and C32 cell lines. The results show that the morphonuclear characteristics of melanoma originating from male and female patients are very distinct (P < 0.01). This difference is still more marked (P < 0.0005) when only premenopausal female patients are compared with male patients. The in vitro data show that both DHT and E2 are able to modify markedly (P < 0.001 to P < 0.0001) the nucleus morphometry and chromatin pattern of the three cell lines. Although the mechanism and the physiological outcome are still unknown, the present work shows that there is in vivo and in vitro evidence that the biological behaviour of human melanoma is influenced by sex steroids.

Adult↗